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Abstract
The immune system plays a vital role in regulating tumor growth, and the oncology community has witnessed an exciting resurgence in clinical research to develop effective immunotherapeutic strategies. The utility of these strategies in advanced melanoma has been at the forefront of these developments. In particular, blockade of programmed cell death protein 1 (PD-1) in advanced melanoma has proven to be a most promising new anticancer strategy. Pembrolizumab is a humanized IgG4 anti-PD-1 antibody that exerts its anti-tumor effect through blocking the interaction of the immune inhibitory molecule PD-1 with its ligands. Its effect has been most convincingly demonstrated in the setting of advanced melanoma, with growing evidence of clinical responses across a broad spectrum of other solid and hematological malignancies.
Acknowledgement
SS Kumar thanks the Simon Kerr Foundation that supported his position as the Melanoma Fellow at the Chris O'Brien Lifehouse.
Financial & competing interests disclosure
CM McNeil sits on a MSD advisory board and has received conference travel support from MSD. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Exciting results from clinical studies demonstrating durable clinical responses following treatment with anti-PD-1 and PD-L1 antibodies in patients with previously refractory malignancies have heightened interest in immunotherapy and immune checkpoint blockade.
Pembrolizumab is a potent and highly selective, humanized anti-PD-1 mAb of the IgG4/kappa isotype that is designed to block the negative immune regulatory signaling of the PD-1 receptor.
Published response rates for anti-PD-1 therapy, coupled with reported response durability and a favorable toxicity profile, have placed this new class of immune checkpoint inhibitor at the forefront of systemic therapies for metastatic melanoma.
Given that not all patients respond to these therapies, future directions will focus on identifying predictors of response and toxicity, and on evaluating PD-1 blockade in combination with other immunotherapeutic approaches, radiotherapy, chemotherapy and both existing and novel small molecule targeted therapy.